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Biomedical subjects

F Richards

Publications and source records attributed to F Richards.

At least 127 records · Page 7Linked to original sources
PubMed1982

Nonseminomatous germ cell cancer of the testis. Reducing treatment-related morbidity in patients with disseminated disease.

Fourteen previously untreated patients with metastatic nonseminomatous germ cell cancer of the testis (NSGC) were treated with a modified VAB-4 regimen which was designed to reduce treatment-related morbidity. Nine of 10 patients with minimal disease and the only patient with advanced pulmonary disease achieved a complete response (CR) with chemotherapy alone. Two of three partial responders with advanced abdominal disease were converted to CR status with radiotherapy and/or surgery. None of the 12 CRs have relapsed (median duration of follow-up, 28+ months). We observed no granulocytopenic fever or permanent renal insufficiency. These results indicate that NSGC patients with a low tumor burden can be spared substantial toxicity without adversely affecting complete response rates.

Antineoplastic Agents↗
PubMed1982

Nonseminomatous germ-cell cancer of the testis.

Fourteen previously untreated patients with metastatic nonseminomatous germ-cell cancer of the testis (NSGC) were treated with a modified VAB-4 regimens that was designed to reduce treatment-related morbidity. Nine of ten patients with minimal disease and the only patient with advanced pulmonary disease achieved a complete response (CR) with chemotherapy alone. Two of three partial responders with advanced abdominal disease were converted to CR status with radiotherapy and/or surgery. None of the 12 CRs has had a relapse (median duration of follow-up, 28+ months). We observed no granulocytopenic fever or permanent renal insufficiency. These results indicate that NSGC patients with a low tumor burden can be spared substantial toxicity without the complete response rates being adversely affected.

Antineoplastic Agents↗
PubMed1982

Combination chemotherapy-radiotherapy with and without the methanol-extraction residue of Bacillus Calmette-Guerin (MER) in small cell carcinoma of the lung: a prospective randomized trial of the Piedmont Oncology Association.

The effect of addition of the nonspecific immunostimulant, MER, to combined treatment with chemotherapy and radiotherapy in small cell carcinoma of the lung was evaluated in a prospective randomized trial involving 102 evaluable patients. Chemotherapy consisted of cyclophosphamide, Adriamycin, vincristine, methotrexate, and CCNU; and radiotherapy was administered to the primary lesion, mediastinum, supraclavicular areas, and whole brain. Of 47 patients administered MER 400 mcg intradermally every six weeks, 12 (26%) attained complete remission with a median survival of 22.9 months. Complete remission was observed in 17 (31%) of 55 patients who received no MER with a median survival of 20.0 months (P greater than 0.05). Survival greater than or equal to 2 years has been observed in five patients who received MER and two patients who did not receive MER. The response rate and duration, survival, and toxicity of the two treatment arms were similar with the exception of cutaneous and occasional systemic reaction to MER. MER as used in this study has not influenced the overall results of a combined modality treatment program for patients with small cell carcinoma of the lung.

Adult↗
PubMed1982

Effect of methanol extraction residue of Bacillus Calmette-Guerin in advanced Hodgkin's disease.

One-hundred-ninety-six patients with Stage III and IV Hodgkin's disease were prospectively randomized to receive either treatment with the methanol extraction residue of Bacillus Calmette-Guerin (MER/BCG) or no immunotherapy. Prior to the MER/BCG randomization, patients received six courses of induction and two years of maintenance chemotherapy so that a group with a presumptively low tumor burden could be established. Only patients achieving a complete remission were evaluated. During the first two years of immunotherapy, the MER/BCG group had a relapse frequency twice that of controls. The overall crude relapse frequency and disease-free survival were similar between the two treatment groups. The MER/BCG dose schedule used in this study was associated with a high frequency of unacceptable toxicity. Ulcerations of greater than 1 cm occurred in one-third of the patients with associated pain, fever, and occasional lymphadenopathy. A high degree of patient noncompliance (36%) was observed. Age (P = 0.002), prior radiotherapy (P = 0.032), and chemotherapy (P = 0.044) were prognostic factors found to significantly influence remission duration. These factors were balanced between patients treated with immunotherapy and those who were not. MER/BCG therapy did not significantly delay or prevent relapse.

Adult↗
PubMed1982

Severe neurotoxicity with methyl G: CALGB experience.

Methylglyoxal bis-dihydrochloride is a drug that has been available for use in cancer chemotherapy since 1955. In earlier studies, it was used on a daily schedule with resulting severe gastrointestinal toxicity and myelosuppression. To avoid that toxicity, a new weekly schedule has been adopted in several Phase II studies. With the weekly schedule, new types of toxicity have been described and we report four patients who have developed a severe sensory-motor neuropathy with the chemotherapy which appears to be drug-related.

Aged↗
PubMed1981

Intravenous vincristine infusion: phase I trial.

In an attempt to sustain potentially cytotoxic concentrations of vincristine in man, a five-day continuous infusion of vincristine after an initial intravenous bolus injection was administered to 30 patients with refractory malignancies. Three dosage levels were explored (0.5 mg/m2, 0.75 mg/m2, and 1.0 mg/m2 daily for five days). Neurologic and hematologic toxicity were severe at the high dose level, whereas mild to moderate toxicity occurred at the 0.5 and 0.75 mg/m2 dose levels. Objective responses were noted in 11 patients (37%) with the following malignancies: non-Hodgkin's lymphoma (4), acute non-lymphoblastic leukemia (2), chronic granulocytic leukemia in blast crisis (1), carcinoma of the breast (3), and small cell carcinoma of the lung (1). Responses were observed at each infusion dose level. Nine of the 11 responders had previously progressed while receiving conventional intravenous bolus injection of vincristine. These data suggest that the clinical usefulness of vincristine may be enhanced by the use of infusion techniques. A maximum daily dose of 0.5 mg/m2 given for five days is recommended for future trials of intravenous vincristine infusion.

Aged↗
PubMed1981

Chemotherapy of advanced ovarian epithelial carcinoma with melphalan and levamisole: a pilot study of the Gynecologic Oncology Group.

Twenty-three patients with Stage III, Stage IV, or recurrent epithelial ovarian cancer were treated with a combination of melphalan and levamisole to determine a tolerable dosage schedule, possible adverse effects, and a general estimate of response rate and duration. In seven patients with measurable disease there were four complete responses (57%) with a median duration of 75 weeks. Two of the complete responders have had negative second-look laparotomies while the other two patients have had subsequent progression. Of 16 patients with nonmeasurable disease two have had negative second-look laparotomies and two remain progression free. Thus 8 of 23 patients (35%) had complete responses or remain progression free whereas 4 of 23 patients (17%) have had negative second-look laparotomies. No serious toxicity was encountered. Immunologic monitoring did not indicate significant immunologic reconstitution in these immunosuppressed patients.

B-Lymphocytes↗
PubMed1981

Combination chemotherapy with and without the methanol-extracted residue of bacillus Calmette-Guerin (MER) in extensive non-small-cell lung cancer: a prospective randomized study for the Piedmont Oncology Association.

One-hundred-three patients with extensive non-small-cell lung cancer were entered into a prospective, randomized trial to determine the value of MER as an adjuvant to chemotherapy. Patients were stratified according to histology and performance status. All patients received CCNU, methotrexate, and Adriamycin with 48 patients also receiving MER. All patients had a performance status of 2 or less (less than 50% bedridden), 49% had prior radiation therapy, only one patient had prior chemotherapy, and all had extensive disease. Of the patients, 42% had epidermoid cancer, 21% had large cell cancer, 32% had adenocarcinoma, and 4% had mixed adenosquamous or undifferentiated carcinoma. The response rates and response durations of the two treatment regimens were similar. Of the patients, 18% had an objective response; in 4% it was complete. An additional 29% had a stable response. Median duration of response ranged from 21 to 23 weeks. Median survival rates for non-MER and MER treatment groups were 21.5 and 18.6 weeks, respectively. The four complete responders have a survival of 24, 85, 86+, and 129 weeks. MER did not improve response for hematopoietic tolerance, was associated with significant morbidity, and was poorly tolerated. The value of immunotherapy in lung cancer remains to be established.

Adenocarcinoma↗
PubMed1981

A randomized comparative trial of chemotherapy and irradiation therapy for stage II breast cancer.

One hundred fifty-eight evaluable patients with Stage II carcinoma of the breast with positive lymph nodes were treated either with adjuvant chemotherapy or irradiation therapy followed by chemotherapy. Patients were randomized to test the effectiveness of L-phenylalanine mustard (L-PAM) with and without postoperative irradiation therapy (R.T.) against cyclophosphamide, 5-fluorouracil, and methotrexate (CMF) with and without postoperative irradiation therapy in decreasing the frequency of recurrence. No significant difference was observed between L-PAM as compared with R.T. plus L-PAM (P = 0.85). The difference between CMF and R.T. plus CMF was significant in support of CMF alone (P = 0.04). The frequency of recurrence between R.T. plus L-PAM and R.T. plus CMF showed no difference. A comparison of the chemotherapy only regimens showed an advantage of CMF over L-PAM (P = 0.05). Both the delay in starting chemotherapy and the significant decrease in percent optimal drug dosage during the first six cycles of therapy are factors that may influence the high frequency of relapse observed in the R.T. plus chemotherapy groups. Of the four treatments, CMF has the lowest frequency of recurrence.

Adult↗
PubMed1981

Chemotherapy vs. chemoimmunotherapy with methanol extraction residue of Bacillus Calmette-Guerin (MER) in advanced breast cancer: a randomized trial by the Piedmont Oncology Association.

Effects of the addition of MER, a nonspecific, nonviable immunostimulant, to two combination chemotherapy programs were explored in patients with metastatic breast cancer. Patients were randomized to either CDVFP [cyclophosphamide (C), doxorubicin (D), vincristine (V), fluorouracil (F) and prednisone (P)] or CD alternating with methotrexate (M) and F (CD/MF). Each group was also randomized to receive MER, 0.4 mg S.C. every four weeks or no immunotherapy. The response rates were CDVFP 56%, CDVFP + MER 54%, CD/MF 43%, and CD/MF + MER 43%. No significant differences were noted in response rate. Median durations of response and survival were similar for each group: CDVFP 16.2 and 25.2 months, respectively; CDVFP + MER 14.0 and 23.3 months, CD/MF 12.1 and 26.1 months, and CD/MF + MER 15.5 and 25.6 months. Patients who achieved CR frequently had soft-tissue disease (7/17) and patients with disease in 1 or 2 metastatic sites had a significantly higher response rate than those in greater than or equal to 3 sites. MER did not enhance response rate, duration of response, or survival. Also MER did not diminish myelosuppression.

Antineoplastic Agents↗
PubMed1981

Cyclophosphamide versus cyclophosphamide, methotrexate, and 5-fluorouracil in advanced prostatic cancer: a randomized trial.

Thirty-two evaluable patients with metastatic carcinoma of the prostate were entered into a prospective randomized trial comparing cyclophosphamide (CYC) with a combination of cyclophosphamide, methotrexate, and fluorouracil (CMF). Progressive disease after endocrine manipulation was noted in 97% (31/32) of patients before entry. Stable disease (S) was observed in 9 of 17 patients treated with CYC. One partial response (PR) and seven stable responses occurred in the 15 CMF patients. Median duration of stable response was 4.5 months for CYC and 4.5 months on CMF. Median survival of patients with PR and S receiving CYC was 10.1 and for CMF 8.8 months. Patients with progressive disease survived a median 1.7 and 2.6 months with CYC and CMF, respectively. Toxicity was moderate, and no deaths were attributable to sepsis or bleeding. Almost all patients in this study had bone lesions as the dominant site of disease; this made objective assessment of response difficult. There was no significant improvement in response conferred by the combination regimen. Although patients with metastatic prostatic cancer may benefit from chemotherapy, impressive clinical responses are uncommon.

Aged↗
PubMed1981

A prospective study of histocompatible leukocyte and platelet transfusions during induction chemotherapy of adult acute nonlymphocytic leukemia.

A prospective clinical trial was conducted to test the effectiveness of granulocyte transfusions during induction chemotherapy of patients with adult acute non-lymphocyte leukemia. Thirty-eight patients who received prophylactic granulocyte transfusions from related donors when their phagocyte counts decreased to less than 1000 microliter were compared to twenty-five controls who did not have qualified donors from which to obtain granulocyte transfusions. The frequency of complete remissions (CR) (28/38 versus 7/25) was significantly greater for the granulocyte transfusion group than for controls. Patients older than 45 responded more often in the transfused group (P less than 0.025) when compared to the similar age group in controls. Both duration of complete remission and survival were greater in the granulocyte transfused group. However, these differences were not statistically significant. Survival for all responders (complete plus partial remission) was longer for the granulocyte transfusion group (P = 0.01). No significant difference in frequency or severity of either infection or hemorrhage was noted in the two groups. The advantage noted in this study largely occurred in patients older than 45 and this suggests that this age group is more likely to respond if they have histocompatible donors from which to obtain granulocyte and platelet transfusions. Immune mechanisms may be involved in the beneficial effects observed with HLA compatible granulocyte transfusions.

Adolescent↗
PubMed1981

Intraventricular hemorrhage from pituitary apoplexy.

The case of a patient with a massive intraventricular hemorrhage arising from a pituitary chromophobe adenoma is described. This rare and disastrous complication was ascribed to the large suprasellar extension of the tumor and its close proximity to the floor of the third ventricle. Hemorrhage in the tumor extended along the path of least resistance and ruptured into the third ventricle. A partially treated hyperviscosity syndrome and chemotherapy for an unrelated malignancy (multiple myeloma) may have predisposed the patient to the necrosis and hemorrhage in the pituitary tumor.

Adenoma↗
PubMed1981

Pharmacokinetics of vincristine sulfate in adult cancer patients.

Vincristine concentration in serum from 1 min to 72 hr was measured by radioimmunoassay in 14 patients with cancers following i.v. bolus injection of vincristine sulfate at 0.45 to 1.30 mg/sq m. The pharmacokinetic data were analyzed by a nonlinear least-square regression program NONLIN. A three-compartmental open model fitted the raw data better than a two-compartmental model. The mean half-lives of the triphasic decay curves alpha, beta, and gamma were 1.9, 19.2, and 1359 min (22.6 hr), respectively. The apparent volume of the central compartment and the volume of distribution at steady state (Vdss) per 1.73 sq m body surface area were 4.1 and 167.6 liters, respectively. The plasma clearance was 141.9 ml/min/1.73 sq m, and the area under the concentration X time curve from 0 to infinity (AUC0 infinity) for 2 mg vincristine was 21,689 nM.min. Linear regression analysis of the data gave evidence for increasing plasma clearance at higher doses of vincristine. In patients with higher platelet counts, lower AUC0 infinity values were obtained, suggesting a possible interaction of vincristine with blood platelets. Our results, a large Vdss, a long biological half-life, and a low rate-limiting rate constant from Compartment 3 to the central compartment (k31), indicate an avid tissue binding and a slow drug release from the body tissues which may account for drug-related neurotoxicity.

Adult↗
PubMed1980

Advanced epidermoid lung cancer: prolonged survival after chemotherapy.

The charts and pathologic reports for 4 patients seen at our institution with advanced incurable epidermoid carcinoma of the lung, who had prolonged disease-free survival after chemotherapy, were reviewed. All patients had Stage III bronchogenic carcinoma. Our study indicates that patients with epidermoid carcinoma of the lung who achieve a complete response have a better survival than those patients who have a partial response or no response. All complete responses were achieved after two to three months of chemotherapy, and if a response is not seen by then a modification of the treatment program is recommended. We propose that complete response should be considered the most important prognostic factor for therapeutic trials in epidermoid carcinoma of the lung.

Antineoplastic Agents↗
PubMed1980

Therapy of advanced colorectal carcinoma with 5-fluorouracil and cyclophosphamide in combination with either CCNU or methotrexate.

In a prospective, randomized study a combination of 5-FU, Cyclophosphamide, and Methortrexate (FC-MTX) was compared to a similar combination (FC-CCNU) in which CCNU replaced Methotrexate. Of the 54 patients with metastatic colorectal carcinoma entered, 47 were evaluable. Toxicity was similar for the two regimens and was acceptable. No complete responses occurred. No difference in partial response (PR) 2/24 for FC-CCNU vs. 3/23 for FC-MTX, stable response 16/47 overall, or progressive disease 26/47 overall, was observed. Duration of PR was three to ten months. The overall median survival was six months, three months for non-responders and 11 months for responders. These drug combinations employing 5-FU do not improve upon the results reported with 5-FU alone in the treatment of metastatic colorectal carcinoma.

Adenocarcinoma↗